In this application for a KO1 Mentored Research Scientist Development Award, Dr. Ziva Cooper has proposed a comprehensive plan to integrate a training plan towards becoming an independent researcher in the field of human behavioral pharmacology with her interest in investigating human laboratory models of polysubstance abuse. Substances are rarely abused independently, thus, determining the physiological and behavioral effects, and the health risks associated with abused drugs administered independently and simultaneously under well-controlled conditions is an imperative preliminary step to advance the area of substance-abuse treatment. Abuse of marijuana among the cocaine-dependent population is widespread. Although there has been a great deal of research advancing the treatment of cocaine and marijuana dependence independently, there have been no studies investigating potential treatments for dependence on both substances. Understanding the precise nature of the interaction between marijuana and cocaine is an essential first step to developing pharmacotherapy strategies for their co-abuse. The research aims of the proposed studies are to first determine the behavioral and physiological effects of experimenter-administered marijuana in combination with smoked cocaine that contribute to the abuse liability and health risks associated with the drug combination. Next, the influence of marijuana on relapse to smoked cocaine self-administration will be determined using a human laboratory relapse model. The training goals for Dr. Cooper are to 1) acquire a more comprehensive knowledge of methodology, safety, and ethics of conducting research with psychoactive substances in the human laboratory; 2) gain expertise in methodology and data analysis for research on experimenter and self-administered marijuana and smoked cocaine in the human laboratory 3) research contemporary statistical approaches to human laboratory research 4) increase proficiency in manuscript and grant writing. Overall, this award will ensure Dr. Cooper's successful transition to an independent investigator in the field of human behavioral pharmacology of substance use disorders. PUBLIC HEALTH RELEVANCE: Despite the prevalence of polysubstance abuse among the drug-using population, little is known about the increased abuse liability and health risks associated with popular drug combinations. Marijuana dependence and abuse among the cocaine-dependent population is a well-established phenomenon, yet there have been no studies investigating the influence of marijuana on relapse to cocaine use. These studies will fill a critical gap in medications development for substance-use disorders by determining the behavioral and physiological effects of marijuana smoked with cocaine.